Casar Juan Carlos, McKechnie Beth A, Fallon Justin R, Young Marian F, Brandan Enrique
Centro de Regulación Celular y Patología, Facultad de Ciencias Biológicas, MIFAB P. Universidad Católica de Chile, Santiago, Chile.
Dev Biol. 2004 Apr 15;268(2):358-71. doi: 10.1016/j.ydbio.2003.12.025.
The onset and progression of skeletal muscle regeneration are controlled by a complex set of interactions between muscle precursor cells and their environment. Decorin is the main proteoglycan present in the extracellular matrix (ECM) of adult muscle while biglycan expression is lower, but both are increased in mdx mice dystrophic muscle. Both of these small leucine-rich proteoglycans (SLRPs) can bind other matrix proteins and to the three TGF-beta isoforms, acting as modulators of their biological activity. We evaluated biglycan and decorin expression in skeletal muscle during barium chloride-induced skeletal muscle regeneration in mice. A transient and dramatic up-regulation of biglycan was associated with newly formed myotubes, whereas decorin presented only minor variations. Studies both in vitro and in intact developing newborn mice showed that biglycan expression is initially high and then decreases during skeletal muscle differentiation and maturation. To further evaluate the role of biglycan during the regenerative process, skeletal muscle regeneration was studied in biglycan-null mice. Skeletal muscle maintains its regenerative capacity in the absence of biglycan, but a delay in regenerated fiber growth and a decreased expression of embryonic myosin were observed despite to normal expression of MyoD and myogenin. Transient up-regulation of decorin during muscle regeneration in these mice may possibly obscure further roles of SLRPs in this process.
骨骼肌再生的起始和进程受肌肉前体细胞与其环境之间一系列复杂相互作用的控制。核心蛋白聚糖是成年肌肉细胞外基质(ECM)中存在的主要蛋白聚糖,而双糖链蛋白聚糖的表达较低,但在mdx小鼠的营养不良肌肉中两者均会增加。这两种富含亮氨酸的小分子蛋白聚糖(SLRPs)都能与其他基质蛋白以及三种转化生长因子-β(TGF-β)亚型结合,作为其生物活性的调节剂。我们评估了氯化钡诱导的小鼠骨骼肌再生过程中双糖链蛋白聚糖和核心蛋白聚糖在骨骼肌中的表达。双糖链蛋白聚糖的短暂且显著上调与新形成的肌管有关,而核心蛋白聚糖仅有轻微变化。体外和完整发育的新生小鼠体内研究均表明,双糖链蛋白聚糖的表达最初较高,然后在骨骼肌分化和成熟过程中降低。为了进一步评估双糖链蛋白聚糖在再生过程中的作用,我们在双糖链蛋白聚糖基因敲除小鼠中研究了骨骼肌再生。在缺乏双糖链蛋白聚糖的情况下,骨骼肌仍保持其再生能力,但尽管肌分化抗原(MyoD)和生肌调节因子(myogenin)表达正常,仍观察到再生纤维生长延迟以及胚胎肌球蛋白表达降低。在这些小鼠的肌肉再生过程中,核心蛋白聚糖的短暂上调可能会掩盖SLRPs在此过程中的进一步作用。